What is Antibody-Dependent Enhancement and why should you care.

Posted on by Jesse Santiano, M.D.

Addendum October 18, 2021. A new article adds more mechanisms for antibody-dependent enhancement. Five Mechanisms of Antibody-Dependent Enhancement

Antibody-Dependent Enhancement, ADE

ADE is a phenomenon observed in animals during vaccine development against the coronaviruses and measles, respiratory syncytial virus, and dengue viruses previously.

In ADE, the inoculated animals develop the antibodies, but with time, the neutralizing antibodies decrease. When the animals were exposed to a wild-type coronavirus (to test vaccine effectiveness), instead of being protected the animals developed severe infections and died.

How does ADE happen?

Antibodies are shaped like the letter Y have two major parts, the antigen-binding fragment or Fab and the crystallizable fragment or Fc.

The work of the antibody is mainly done by the Fab part, which attaches to the antigen. In the case of coronaviruses, the neutralizing antibody should attach to the Receptor-binding Domain of the spike protein to form an antigen-antibody complex and prevent its attachment to human cells.

The antigen-antibody complex triggers a complex immune response that leads to the destruction of the virus.

Below is a cryo-electron microscope image of a coronavirus spike protein with the receptor-binding domain in pink. RBD is where a neutralizing antibody should stick to prevent viral entry into the cells and prevent replication.

In ADE, the Fab will attach to the RBD but instead, initiating an immune response to destroy the virus, the Fc part of the antibodies does something weird. It attaches to the macrophages and allows viral entry.

Macrophages, a type of white blood cells, are the first-line defense against viral infections. Macrophages are supposed to “eat” or phagocytose the viruses and begin the immune response. They are like soldiers guarding and patrolling an outpost.

Other immune cells like the monocytes, CD32+ cells, Beta cells, and dendritic cells can also be part of ADE.

After attachment of the Fc part, specifically, the Fc gamma receptor 2 pt or FcγRII, the viruses enter the immune cells and start replicating. This leads to the production of millions of viruses that spread to other cells and organs. Eventually overwhelming the immune system and cause a cytokine storm which is why the animals die.

Another mechanism is when the antibody-antigen complex causes enhanced inflammation by forming immune complexes that deposit in airway tissues and activate different inflammation pathways. This results in airway obstruction and acute respiratory distress syndrome.

Both ADE pathways can occur when non-neutralizing antibodies or antibodies at sub-neutralizing levels bind to viral antigens without blocking or clearing infection.[1]

ADE in other vaccines

ADE is not just a theoretical possibility. Aside from vaccines developed against the Severe Acute Respiratory Syndrom (SARS), Middle Eastern Respiratory Syndrome (MERS), and Feline infectious peritonitis coronaviruses, ADE has happened before in vaccines against the Respiratory Syncytial virus, measles, and dengue vaccine.

In the Philippines, fourteen vaccinated children died from ADE after encountering dengue in the community.

Can ADE happen with the present COVID vaccine?

At this time, there is not enough data to say it will definitely happen. What we can surmise is that the CDC is probably very concerned that it can happen. On August 18, 2021, the  U.S. Department of Health and Human Services (HHS) issued a joint statement. (emphasis are mine)

The available data make very clear that protection against SARS-CoV-2 infection begins to decrease over time following the initial doses of vaccination, and in association with the dominance of the Delta variant, we are starting to see evidence of reduced protection against mild and moderate disease. Based on our latest assessment, the current protection against severe disease, hospitalization, and death could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination rollout. For that reason, we conclude that a booster shot will be needed to maximize vaccine-induced protection and prolong its durability.

It could be that they are just concerned with an increase in breakthrough infections. Still, they are probably concerned that the waning neutralizing antibodies will expose many, including the vulnerable, to ADE.

Take Away Message

I don’t give medical advice on this website. But knowing that ADE is potential, if I would develop COVID-19 symptoms like itchy throat, headaches, muscle pain, or chills, I would immediately get tested and start treatment using the FLCCC protocol.

Read: An Update to FLCCC Treatment Protocol for the Delta Variant and An update to the I-MASK+ Prevention & Early Outpatient Treatment Protocol for COVID-19

I will wear a mask if I have to be in a crowded indoor environment with unknown people and wash or disinfect my hands all the time.

The big question about ADE is, If the antibodies wane over 6-8 months, does that mean that booster shots will be required twice a year to prevent ADE?

What’s the consequence of being injected with the mRNA of the spike protein on a bi-yearly basis? Will we see more adverse reactions?

Knowledge about Covid-19 is rapidly evolving. Information may update as new studies are made. Stay current by subscribing. Feel free to share and like.

Don’t Get Sick!

The following are related to antibody-dependent enhancement

  1. Antibodies to the Flu and COVID-19 Cross-React
  2. Antibody dependent enhancement can happen to Delta Variant COVID-19
  3. Antibody-Dependent Enhancement in Breastfed Infants
  4. Antibodies to the Flu and COVID-19 Cross-React

Related:

  1. The Updated List of COVID-19 Articles
  2. Who among the Vaccinated are At Risk of Dying if they get COVID-19?
  3. Highest Viral Loads among Delta Variant compared to other Variants: French Study
  4. 42-day study prompted FDA to approve Moderna booster shots for immune-compromised
  5. Should we be afraid of the delta variant?
  6. Concerning autopsy findings on a patient who had a COVID shot
  7. The Whole English translation of the Spanish study showing 99% Graphene Oxide in the Pfizer COVID-19 Vaccine
  8. Absolute Risk Reduction of the COVID-19 Vaccines. Part 2.
  9. Know the Absolute Risk Reduction of the COVID-19 Vaccines!
  10. The Spike Protein of the SARS-CoV-2 Can Cause Vascular Damage
  11. Myocarditis and the COVID vaccine
  12. Polymerase Theta can Change RNA to DNA
  13. SARS-CoV-2 RNA can Change Human Genes

References:

  1. Ricke DO. Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies. Front Immunol. 2021;12:640093. Published 2021 Feb 24. doi:10.3389/fimmu.2021.640093 [1]
  2. Wan Y, Shang J, Sun S, et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virol. 2020;94(5):e02015-19. Published 2020 Feb 14. doi:10.1128/JVI.02015-19
  3. Lee, W.S., Wheatley, A.K., Kent, S.J., et al. Antibody-dependent enhancement, and SARS-CoV-2 vaccines and therapies. Nat Microbiol 5, 1185–1191 (2020). https://doi.org/10.1038/s41564-020-00789-5
  4. Antibody-dependent enhancement (ADE) and Vaccines. Children’s Hospital of Philadelphia

Image credits:

  1. By 2fab fc.png: User Je at uwo on en.Wikipedia / derivative work: Vezixig – 2fab fc.png, Public Domain, https://commons.wikimedia.org/w/index.php?curid=12247609
  2. RBD by By 5-HT2AR – Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=88638800
  3. ADE By Jmarchn – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=97988895

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